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A non-invasive laboratory panel as a diagnostic and prognostic biomarker for thrombotic microangiopathy: development and application in a Chinese cohort study.

Zhang T, Chen H, Liang S, Chen D, Zheng C, Zeng C, Zhang H, Liu Z - PLoS ONE (2014)

Bottom Line: A panel of 4 variables - creatinine, platelets, ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats 13) activity and LDH - can effectively discriminate patients with TMA (AUC = 0.800).The discrimination effects of these three markers were confirmed in patients with SLE.Among patients undergoing repeat biopsy, increased LDH levels and panel signatures were associated with TMA status when paired evaluations were performed.

View Article: PubMed Central - PubMed

Affiliation: National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, P. R. China.

ABSTRACT

Background: Thrombotic microangiopathy (TMA) in the kidney is a histopathologic lesion that occurs in a number of clinical settings and is often associated with poor renal prognosis. The standard test for the diagnosis of TMA is the renal biopsy; noninvasive parameters such as potential biomarkers have not been developed.

Methods: We analyzed routine parameters in a cohort of 220 patients with suspected TMA and developed a diagnostic laboratory panel by logistic regression. The levels of candidate markers were validated using an independent cohort (n = 46), a cohort of systemic lupus erythematosus (SLE) (n = 157) and an expanded cohort (n = 113), as well as 9 patients with repeat biopsies.

Results: Of the 220 patients in the derivation cohort, 51 patients with biopsy-proven TMA presented with a worse renal prognosis than those with no TMA (P = 0.002). Platelet and L-lactate dehydrogenase (LDH) levels showed an acceptable diagnostic value of TMA (AUC = 0.739 and 0.756, respectively). A panel of 4 variables - creatinine, platelets, ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats 13) activity and LDH - can effectively discriminate patients with TMA (AUC = 0.800). In the validation cohort, the platelet and LDH levels and the 4-variable panel signature robustly distinguished patients with TMA. The discrimination effects of these three markers were confirmed in patients with SLE. Moreover, LDH levels and the 4-variable panel signature also showed discrimination values in an expanded set. Among patients undergoing repeat biopsy, increased LDH levels and panel signatures were associated with TMA status when paired evaluations were performed. Importantly, only the 4-variable panel was an independent prognostic marker for renal outcome (hazard ratio = 3.549; P<0.001).

Conclusions: The noninvasive laboratory diagnostic panel is better for the early detection and prognosis of TMA compared with a single parameter, and may provide a promising biomarker for clinical application.

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Related in: MedlinePlus

Receiver operating characteristic curves and calibration curve for a diagnostic panel.(A) The diagnostic panel was developed in the derivation group of 220 suspected patients, with AUC 0.800, P<0.001. (B) This marker was validated in 46 independent patients, with AUC 0.815, P<0.001. (C) Bootstrap validation shows the calibration curve of the diagnostic panel. Cross-validated estimates of the AUC, calibration-curve intercept and slope were 0.777, 0.07 and 0.64, respectively. The loess-smoothed estimates of the cross-validated and unadjusted calibration curves are overlaid on a diagonal reference line representing good model calibration.
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pone-0111992-g003: Receiver operating characteristic curves and calibration curve for a diagnostic panel.(A) The diagnostic panel was developed in the derivation group of 220 suspected patients, with AUC 0.800, P<0.001. (B) This marker was validated in 46 independent patients, with AUC 0.815, P<0.001. (C) Bootstrap validation shows the calibration curve of the diagnostic panel. Cross-validated estimates of the AUC, calibration-curve intercept and slope were 0.777, 0.07 and 0.64, respectively. The loess-smoothed estimates of the cross-validated and unadjusted calibration curves are overlaid on a diagonal reference line representing good model calibration.

Mentions: The ROC curve showed that this 4-variable model yielded an AUC of 0.800 (95% confidence interval [CI], 0.723 to 0.877; P<0.001), suggesting a good discrimination between patients with TMA in the kidney and those without TMA (Figure 3A). With the use of the cutoff point of 0.248, this diagnostic panel has 81.6% sensitivity and 66.9% specificity. The diagnostic panel for the prediction of TMA was validated in the independent cohort, with an AUC of 0.815 (P<0.001; Figure 3B). The use of the cut-off of 0.248 predicted the presence of TMA with 80.0% sensitivity and 61.5% specificity.


A non-invasive laboratory panel as a diagnostic and prognostic biomarker for thrombotic microangiopathy: development and application in a Chinese cohort study.

Zhang T, Chen H, Liang S, Chen D, Zheng C, Zeng C, Zhang H, Liu Z - PLoS ONE (2014)

Receiver operating characteristic curves and calibration curve for a diagnostic panel.(A) The diagnostic panel was developed in the derivation group of 220 suspected patients, with AUC 0.800, P<0.001. (B) This marker was validated in 46 independent patients, with AUC 0.815, P<0.001. (C) Bootstrap validation shows the calibration curve of the diagnostic panel. Cross-validated estimates of the AUC, calibration-curve intercept and slope were 0.777, 0.07 and 0.64, respectively. The loess-smoothed estimates of the cross-validated and unadjusted calibration curves are overlaid on a diagonal reference line representing good model calibration.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4221199&req=5

pone-0111992-g003: Receiver operating characteristic curves and calibration curve for a diagnostic panel.(A) The diagnostic panel was developed in the derivation group of 220 suspected patients, with AUC 0.800, P<0.001. (B) This marker was validated in 46 independent patients, with AUC 0.815, P<0.001. (C) Bootstrap validation shows the calibration curve of the diagnostic panel. Cross-validated estimates of the AUC, calibration-curve intercept and slope were 0.777, 0.07 and 0.64, respectively. The loess-smoothed estimates of the cross-validated and unadjusted calibration curves are overlaid on a diagonal reference line representing good model calibration.
Mentions: The ROC curve showed that this 4-variable model yielded an AUC of 0.800 (95% confidence interval [CI], 0.723 to 0.877; P<0.001), suggesting a good discrimination between patients with TMA in the kidney and those without TMA (Figure 3A). With the use of the cutoff point of 0.248, this diagnostic panel has 81.6% sensitivity and 66.9% specificity. The diagnostic panel for the prediction of TMA was validated in the independent cohort, with an AUC of 0.815 (P<0.001; Figure 3B). The use of the cut-off of 0.248 predicted the presence of TMA with 80.0% sensitivity and 61.5% specificity.

Bottom Line: A panel of 4 variables - creatinine, platelets, ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats 13) activity and LDH - can effectively discriminate patients with TMA (AUC = 0.800).The discrimination effects of these three markers were confirmed in patients with SLE.Among patients undergoing repeat biopsy, increased LDH levels and panel signatures were associated with TMA status when paired evaluations were performed.

View Article: PubMed Central - PubMed

Affiliation: National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, P. R. China.

ABSTRACT

Background: Thrombotic microangiopathy (TMA) in the kidney is a histopathologic lesion that occurs in a number of clinical settings and is often associated with poor renal prognosis. The standard test for the diagnosis of TMA is the renal biopsy; noninvasive parameters such as potential biomarkers have not been developed.

Methods: We analyzed routine parameters in a cohort of 220 patients with suspected TMA and developed a diagnostic laboratory panel by logistic regression. The levels of candidate markers were validated using an independent cohort (n = 46), a cohort of systemic lupus erythematosus (SLE) (n = 157) and an expanded cohort (n = 113), as well as 9 patients with repeat biopsies.

Results: Of the 220 patients in the derivation cohort, 51 patients with biopsy-proven TMA presented with a worse renal prognosis than those with no TMA (P = 0.002). Platelet and L-lactate dehydrogenase (LDH) levels showed an acceptable diagnostic value of TMA (AUC = 0.739 and 0.756, respectively). A panel of 4 variables - creatinine, platelets, ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats 13) activity and LDH - can effectively discriminate patients with TMA (AUC = 0.800). In the validation cohort, the platelet and LDH levels and the 4-variable panel signature robustly distinguished patients with TMA. The discrimination effects of these three markers were confirmed in patients with SLE. Moreover, LDH levels and the 4-variable panel signature also showed discrimination values in an expanded set. Among patients undergoing repeat biopsy, increased LDH levels and panel signatures were associated with TMA status when paired evaluations were performed. Importantly, only the 4-variable panel was an independent prognostic marker for renal outcome (hazard ratio = 3.549; P<0.001).

Conclusions: The noninvasive laboratory diagnostic panel is better for the early detection and prognosis of TMA compared with a single parameter, and may provide a promising biomarker for clinical application.

Show MeSH
Related in: MedlinePlus